Small, dense LDL particles predict changes in intima media thickness and insulin resistance in men with type 2 diabetes and prediabetes--a prospective cohort study

PLoS One. 2013 Aug 8;8(8):e72763. doi: 10.1371/journal.pone.0072763. eCollection 2013.

Abstract

The association of small, dense low-density lipoprotein (sdLDL) particles with an increased cardiovascular risk is well established. However, its predictive value with regard to glucose metabolism and arterial disease in patients with type 2 diabetes has not been thoroughly investigated. We conducted a prospective longitudinal cohort study in patients with (pre)diabetes who were seen at baseline and after two years. sdLDL particles were determined by gradient gel electrophoresis. Insulin resistance was estimated by using the homeostatic model assessment 2 (HOMA2). Intima media thickness (IMT) and flow-mediated dilation (FMD) were assessed by ultrasound measurements. Fifty-nine patients (mean age 63.0 ± 12.2 years) were enrolled and 39 were seen at follow-up. IMT increased in the whole cohort during follow-up. The change in IMT was predicted by the proportion of sdLDL particles at baseline (p=0.03), and the change in FMD was predicted by LDL-cholesterol levels at baseline (p=0.049). HOMA2 and changes in HOMA2 correlated with the proportion of sdLDL particles and changes in this proportion, respectively (p<0.05 for both). Serum resistin levels increased in parallel with the increasing sdLDL particle number, while serum adiponectin increased only in patients with unaltered sdLDL particle number at follow-up (p<0.01 for both). In conclusion, the proportion of small, dense LDL particles and changes in this proportion are predictive of changes in intima media thickness and insulin resistance, and are closely associated with other determinants of an adverse metabolic status. Thus, this parameter extends the individual risk assessment beyond the limitations of traditional risk markers in patients with dysglycemia.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / blood
  • Aged
  • Carotid Arteries / pathology
  • Carotid Intima-Media Thickness
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / diagnosis
  • Humans
  • Insulin Resistance
  • Lipoproteins, LDL / blood*
  • Male
  • Middle Aged
  • Particle Size
  • Prediabetic State / blood*
  • Prediabetic State / complications*
  • Prediabetic State / diagnosis
  • Prospective Studies
  • Vascular Diseases / blood*
  • Vascular Diseases / complications*
  • Vascular Diseases / diagnosis
  • Vascular Diseases / pathology

Substances

  • Adiponectin
  • Lipoproteins, LDL

Grant support

This study was supported in part by the Swiss National Science Foundation (grant no 32003B-105258 to KB) and an unrestricted grant from AstraZeneca, Switzerland. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.